Tumor Exosomes Research Articles

Non-endoscopic Screening for Esophageal Squamous Cell Carcinoma: Recent Advances.

Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in the gastrointestinal tract, andChina has a high incidence area with a high burden on the disease. As early symptoms of ESCC are not obvious, themortality rate is high, and it is often diagnosed in the intermediate and advanced stages. However, early screeningand treatment may reduce morbidity and mortality. Screening methods are divided into endoscopic and non-endoscopic screening. Endoscopic screening cannot be widely used because of its invasive nature and high cost. Currently, non-endoscopicscreening consists primarily of tumor biomarkers and cytology, and tumor biomarkers including autoantibodies,circulating tumor cells, circulating tumor DNA, exosomes and serum metabolomics are more likely to be effective. Butthe efficiency of early diagnosis of esophageal cancer is low and the accuracy of screening needs to be improved.The aim of this study is to summarize advances in non-endoscopic esophageal cancer screening and strategies toprovide a scientific basis and research idea for esophageal cancer prevention and control. Non-endoscopic screening is better than endoscopic screening. And the application of tumor biomarkers is muchbetter than other non-endoscopic screening methods.

Landscape of tumor and immune system cells-derived exosomes in lung cancer: mediators of antitumor immunity regulation.

The immune system plays a critical role in cancer, including lung cancer, which is the leading cause of cancer-related deaths worldwide. Immunotherapy, particularly immune checkpoint blockade, has revolutionized the treatment of lung cancer, but a large subset of patients either do not respond or develop resistance. Exosomes, essential mediators of cell-to-cell communication, exert a profound influence on the tumor microenvironment and the interplay between cancer and the immune system. This review focuses on the role of tumor-derived exosomes and immune cells-derived exosomes in the crosstalk between these cell types, influencing the initiation and progression of lung cancer. Depending on their cell of origin and microenvironment, exosomes can contain immunosuppressive or immunostimulatory molecules that can either promote or inhibit tumor growth, thus playing a dual role in the disease. Furthermore, the use of exosomes in lung cancer immunotherapy is discussed. Their potential applications as cell-free vaccines and drug delivery systems make them an attractive option for lung cancer treatment. Additionally, exosomal proteins and RNAs emerge as promising biomarkers that could be employed for the prediction, diagnosis, prognosis and monitoring of the disease. In summary, this review assesses the relationship between exosomes, lung cancer, and the immune system, shedding light on their potential clinical applications and future perspectives.

Trends in research of exosomes associated with breast cancer over the past decade: a scientometric analysis.

Breast cancer remains a significant global health challenge, accounting for 2.3 million new cases in 2020 and ranking as the most prevalent cancer by incidence and the fourth in cancer-related mortality worldwide. In China, breast cancer also rapidly increases incidence and burden. The research of exosomes in breast cancer has attracted more and more attention and has a rapid development. Recognizing the pivotal role of exosomes in breast cancer research, we have undertaken a comprehensive scientometric analysis of pertinent scholarly articles published over the past decade to elucidate the current research landscape for researchers. In this study, we gathered all pertinent publications from the Web of Science. Biblioshiny (a web interface for Bibliometrix), VOSviewer software, and CiteSpace software were used to analyze the information on publications, including global trends, countries, institutions, journals, authors, keywords, and citations. A total of 1,239 articles and 625 review articles were retrieved. The annual global publication output has an increased trend in recent decades overall. China contributed the most articles. The publications of the USA had the most total link strength. Nanjing Medical University had the most total link strength. The most relevant source was the International Journal of Molecular Sciences. Tang JH contributed the most articles and had the highest H-index, G-index, and total link strength. The most cited document was "Tumor exosome integrins determine organotropic metastasis", with 2730 citations. The basic themes included "exosomes", "expression", "cells", "identification", "biomarkers", and "serum". The keyword "membrane vesicle" had the strongest bursts. The keywords "target", "biology", "suppressor cell", "molecular mechanism", "tumor progression", "inhibitor", and "model" appeared as prominent focal points in current research and active areas of exploration. Over the past decade, exosome research in breast cancer has undergone a discernible evolution, shifting from broader investigations of exosome roles to focused exploration of specific pathways relevant to breast cancer. Notably, the emphasis has extended to the clinical application of exosomes as biomarkers and potential therapeutic agents in breast cancer treatment.

Is a real-time quantifiable liquid biopsy achievable using a microfluidic lab-on-chip ?

Abstract An increasingly relevant functional measurement is a liquid biopsy to assist in the diagnosis of cancers. The existing approach for liquid biopsy is to utilize microfluidic chips for the isolation of circulating tumor cells (CTCs) or exosomes or extracellular vesicles (EV) from patient samples, and then for the analysis of the cargo contained inside the CTCs, exosomes or EVs. However, such an analysis does not provide a real-time liquid biopsy, since there is a long delay between the time of sample collection and the results from the analysis. Microfluidic chip-formats also provide the capability to mimic tissue functions from the analysis of small numbers of cells cultured in the chip. Analysis of the secreted molecules from such cells could provide a measurement of the secretome, which could be analogous to a liquid biopsy. A 3D structural organization of cells in microfluidic chips is usually in the form of organoids or spheroids. The analysis of organoids or spheroids is well-adapted for immunohistochemistry or ELISA-type identification of surface markers, but not for real-time analysis of secreted molecules since the fluid and molecules in the interior volume of the organoid or spheroid is not accessible in real-time. We have recently proposed an alternative novel design for a microfluidic chip format comprising 3D micro-niches that provide a real-time analysis of secretions produced directly from small numbers of cells. The microfluidic chip with 3D micro-niches then analyses the secretions from these monolayers in real-time (“secretome”). The microfluidic chip includes electronic biosensors that provide real-time measurement of secreted molecules. This short review concludes with a proposition for the means to utilize this novel microfluidic chip to function as a real-time and quantifiable diagnostic screening device to differentiate cancerous cells from healthy cells.

SYT7 is a key player in increasing exosome secretion and promoting angiogenesis in non-small-cell lung cancer

Lung cancer is the leading cause of cancer-related mortality, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Our previous study confirmed that synaptotagmin 7 (SYT7) promoted NSCLC metastasis in vivo and in vitro. Studies have shown that SYT7 is an important regulatory molecule of exocytosis in various cells. However, the characteristics of SYT7 across cancers and the function of SYT7 in tumor exosome secretion remain unclear. In this study, we conducted systematic pancancer analyses of SYT7, namely, analyses of expression patterns, diagnostic and prognostic values, genetic alterations, methylation, immune infiltration, and potential biological pathways. Furthermore, we demonstrated that SYT7 increased the secretion of exosomes from A549 and H1299 cells, promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs). Notably, SYT7 promoted angiogenesis by transferring exosomes containing the molecule centrosomal protein of 55 kDa (CEP55) protein to HUVECs. The CEP55 protein levels was downregulated in STAT1 inhibitor-treating SYT7-overexpresion NSCLC cells. We further found that SYT7 activated the mTOR signaling pathway through the downstream molecule CEP55, thereby promoting the invasion and metastasis of NSCLC cells. SYT7 promoted exosome secretion by NSCLC cells through upregulating syntaxin-1a and syntaxin-3. In vivo, SYT7 promoted the tumorigenesis, angiogenesis and metastasis of A549 cells through the exosome pathway. Our study is of great importance for understanding the mechanism of tumor exosome secretion and the role of exosomes in tumor progression.

Salivaomics to decode non-coding RNAs in oral cancer. A narrative review.

Oral cancer is the most debilitating disease which affects the orderly life of a human. With so much advancement in research and technology, the average life expectancy of an individual with oral cancer appears to be about 5 years. The changing trend in incidence of oral cancer among young individuals and women without tobacco habits are ascending. Non habit related oral cancer are taking centre stage and multiple factors which induce complex biology are associated in such scenarios. To decipher the aetiology and to understand the process, these cancerous conditions are to be studied at molecular level. Saliva, the most non-invasively obtained body fluid are assessed for biomarkers exclusively in liquid biopsy. This fluid gives a huge platform to study number of molecules associated with oral cancer. Non coding RNAs are transcripts with no protein coding function. They are gaining more importance in recent times. Long noncoding RNA, microRNA are major types of noncoding transcriptome that influences in progression of oral cancer. They seem to play an important role in health and disease. Apart from these, circulating tumour cells, exosomes, extracellular vesicles, antigens and other proteins can be studied from saliva. This review is aimed to update the knowledge on current biomarkers in saliva associated with oral cancer and their epigenetic role in disease progression as well recent advances in detecting these markers to identify the stage of the disease, which will help in deciding the treatment protocol.

Exosomes derived from ovarian cancer cells regulate proliferation and migration of cancer-associated fibroblasts

Cancer-associated fibroblast (CAF) is an essential risk factor for ovarian cancer. Exosomes can mediate cellular communication in the tumour microenvironment, but the interaction of tumour cell exosomes with CAF is less studied in Ovarian cancer. This study identified H19/miR-29c-3p/LOXL2-COL1A1 as a ceRNA regulatory network involved in regulating tumour matrix-associated signaling pathways associated with CAF. Cellular assays demonstrated that exosomes from ovarian cancer cell line SKOV3 significantly promoted the proliferation and migration of CAF. The results of mixed transplantation tumour experiments in nude mice showed that exosomes of SKOV3 significantly promoted tumour growth. Ovarian cancer tumour-derived exosomes can regulate CAF proliferation and migration through H19/miR-29c-3p/LOXL2-COL1A1. This study reveals the regulatory role of tumour exosomes on CAF, which may provide a theoretical basis for the development of therapeutic regimens targeting fibroblasts in ovarian cancer.

The Emerging Role of Liquid Biopsies in Revolutionising Cancer Diagnosis and Therapy.

A potential non-invasive technique for identifying and tracking cancer is a liquid biopsy. This review article provides a comprehensive overview of the principles, applications, and challenges associated with liquid biopsies. The circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), exosomes, and microRNAs are just a few of the biomarkers we cover in this article that are discovered in liquid biopsies. The clinical application of liquid biopsies in many stages of cancer management, including early cancer identification, therapy selection and response monitoring, and minimum residual illness, is also investigated. The technical advancements in liquid biopsy techniques, including digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS), have improved the sensitivity and specificity of biomarker identification. Liquid biopsies require assistance with cost-effectiveness, sensitivity, and standardisation despite the potential benefits. We talk about these restrictions and potential solutions. In conclusion, liquid biopsies revolutionise personalised therapies and cancer diagnostics by providing a real-time, non-invasive tool for characterising and monitoring tumours. It will be possible to expand the use of liquid biopsies in clinical practises by having a better understanding of their current state and predicted future developments.

Liquid biopsy in ovarian cancer: advantages and limitations for prognosis and diagnosis.

Ovarian cancer (OC) is a highly fatal gynecologic malignancy, often diagnosed at an advanced stage which presents significant challenges for disease management. The clinical application of conventional tissue biopsy methods and serological biomarkers has limitations for the diagnosis and prognosis of OC patients. Liquid biopsy is a novel sampling method that involves analyzing distinctive tumor elements secreted into the peripheral blood. Growing evidence suggests that liquid biopsy methods such as circulating tumor cells, cell-free RNA, circulating tumor DNA, exosomes, and tumor-educated platelets may improve early prognosis and diagnosis of OC, leading to enhanced therapeutic management of the disease. This study reviewed the evidence demonstrating the utility of liquid biopsy components in OC prognosis and diagnosis, and evaluated the current advantages and limitations of these methods. Additionally, the existing obstacles and crucial topics for future studies utilizing liquid biopsy in OC patients were discussed.

The current status of tumor microenvironment and cancer stem cells in sorafenib resistance of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous and aggressive liver cancer that presents limited treatment options. Despite being the standard therapy for advanced HCC, sorafenib frequently encounters resistance, emphasizing the need to uncover the underlying mechanisms and develop effective treatments. This comprehensive review highlights the crucial interplay between the tumor microenvironment, cancer stem cells (CSCs), and epithelial-mesenchymal transition (EMT) in the context of sorafenib resistance. The tumor microenvironment, encompassing hypoxia, immune cells, stromal cells, and exosomes, exerts a significant impact on HCC progression and therapy response. Hypoxic conditions and immune cell infiltration create an immunosuppressive milieu, shielding tumor cells from immune surveillance and hindering therapeutic efficacy. Additionally, the presence of CSCs emerges as a prominent contributor to sorafenib resistance, with CD133+ CSCs implicated in drug resistance and tumor initiation. Moreover, CSCs undergo EMT, a process intimately linked to tumor progression, CSC activation, and further promotion of sorafenib resistance, metastasis, and tumor-initiating capacity. Elucidating the correlation between the tumor microenvironment, CSCs, and sorafenib resistance holds paramount importance in the quest to develop reliable biomarkers capable of predicting therapeutic response. Novel therapeutic strategies must consider the influence of the tumor microenvironment and CSC activation to effectively overcome sorafenib resistance in HCC.

Immobilization-free dual-aptamer-based photoelectrochemical platform for ultrasensitive exosome assay

Exosomes, involved in cancer-specific biological processes, are promising noninvasive biomarkers for early diagnosis of cancer. Herein, an immobilization-free dual-aptamer-based photoelectrochemical (PEC) biosensor was proposed for the enrichment and quantification of cancer exosome based on photoactive bismuch oxyiodide/gold/cadmium sulfide (BiOI/Au/CdS) composites, nucleic acid-based recognition and signal amplification. In this biosensor, the recognition of exosome by two aptamers would trigger the deoxyribonucleotidyl transferase (TdT) enzyme-aided polymerization, leading to the enrichment of alkaline phosphatase (ALP) on Fe3O4 surface. After magnetic separation, ALP could catalyze the generation of ascorbic acid (AA) as electron donor and initiate the following redox cycle reaction for further signal amplification. Furthermore, all the above processes were performed in solution, the recognition and signal amplification efficiency would be superior than the heterogeneous strategy owing to the avoidance of steric hindrance effect. As a result, the proposed PEC biosensor was capable of enriching and detecting of cancer exosomes with high sensitivity and selectivity. The linear range of the biosensor was from 1.0 × 102 particles·μL−1 to 1.0 × 106 particles·μL−1 and the detection limit was estimated to be 21 particles·μL−1. Therefore, the proposed PEC biosensor holds great promise in quantifying tumor exosome for nondestructive early clinical cancer diagnosis and various other bioassay applications.

Electrochemical Detection of Tumor Cell-Derived Exosomes Based on Cyclic Enzyme Scission and Hybridization Chain Reaction Dual-Signal Amplification

Tumor cell-derived exosomes are considered a potential source of cancer biomarkers. Here, we developed an electrochemical sensing platform for the rapid and simple detection of exosomes, using the CCRF-CEM exosome as a model. The platform utilizes cyclic nicking enzyme cleavage and a hybridization chain reaction (HCR) for dual-signal amplification. A hairpin aptamer probe (HAP) containing an aptamer was designed for the assay. The specific binding between the aptamer and PTK7, present on the exosome surface, causes a conformational change in the HAP. This facilitates hybridization between the HAP and the linker DNA, which subsequently triggers cyclic cleavage of the nicking endonuclease towards the linker DNA. Therefore, exosome detection is transformed into DNA detection. By combining this approach with HCR signal amplification, we achieved high-sensitivity electrochemical detection of CCRF-CEM exosomes, down to 1.1 × 104 particles/mL. Importantly, this assay effectively detected tumor exosomes in complex biological fluids, demonstrating the potential for clinical diagnosis.

Hypoxia-induced tumor exosomes promote angiogenesis through miR-1825/TSC2/mTOR axis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is characterized by enhanced angiogenesis resulting in poor prognosis despite improvements in diagnostic/therapeutic techniques. Here, we aimed at investigating potential roles of miR-1825 enclosed in OSCC-derived exosomes on angiogenesis under hypoxic conditions. Effects of miR-1825 mimic/inhibitor as well as hypoxia-induced tumor derived exosomes on human umbilical vein endothelial cells (HUVECs) were evaluated using cell viability, migration/invasion, tube formation, and spheroid-based 3D angiogenesis assays. Hypoxic conditions caused significant increase in miR-1825 levels in OSCC cells and hiTDEs. miR-1825 alone and within hiTDEs promoted endothelial cell viability, migration, invasion, and angiogenic potential, which is reversed via inhibition of miR-1825 expression. miR-1825 within hiTDEs altered the angiogenesis potential of HUVEC cells via deregulation of TSC2/mTOR axis. We showed that hypoxia led to OSCC-derived exosome mediated transfer of miR-1825 to HUVECs and enhanced angiogenesis in OSCC in vitro.

Ultrasensitive detection of exosomes by microchip electrophoresis combining with triple amplification strategies

The analysis of exosomes is significant as they can be used for various pathophysiological processes, especially cancer related intercellular communication. Therefore, a convenient, reliable, and sensitive detection method is urgently needed. Strand displacement amplification (SDA) and catalytic hairpin assembly (CHA) are two kinds of effective isothermal nucleic acid amplification methods. In this article, an efficient quantitative MCE method for detecting human breast cancer cell (MCF-7) exosomes assisted by triple amplification strategies combining cholesterol probe (Chol-probe) with SDA-CHA was first developed. CD63 aptamer was immobilized on the avidin magnetic beads to specifically capture exosomes and then Chol-probe with high affinity was spontaneously inserted into the exosome membrane, which was the first step of amplification strategy to improve detection sensitivity. After magnetic separation, Chol-probe could complement ssDNA and trigger SDA, producing a large number of DNA sequences (Ta) to trigger CHA, achieving SDA-CHA amplification. Under optimal conditions, the detection limit (LOD) for MCF-7 exosomes was as low as 26 particle/μL (S/N = 3). This method provides an effective approach for sensitive and accurate quantification of tumor exosomes, and can be expected to detect exosomes in clinical samples.

An electrochemical aptasensor for exosomes based on strand displacement amplification and hybridization chain reaction amplification

Exosomes are lipid bilayer vesicles, relating to the happening and progress of cancer. However, exploring reliable, convenient and sensitive exosomes detection methods in early cancer diagnosis is still challenging. Here, an electrochemical aptasensor based on both signal amplifications of strand displacement amplification (SDA) and hybridization chain reaction (HCR) was developed to sensitively detect tumor exosomes. Firstly, exosomes were recognized by CD63 aptamer, and converted into DNA concentration by chain replacement reaction and magnetic separation. A produced DNA fragment (P) was obtained by SDA，then P was captured at the modified gold electrode and amplified using HCR. Abundant horseradish peroxidase (HRP) attached to DNA concatemers and catalyzed the oxidation of o-phenylenediamine (OPD). The reduction current of 2,3-diaminopenazine (DAP) was measured and the exosomes were quantized. Under the optimal conditions, the DPV response showed a great linear relationship with exosomes concentration range of 44 ∼ 8.8 × 106 particle/μL. The limit of detection was 18 particle/μL. Experimental results show that this is an alternative method to detect exosomes and other tumor markers.

Dual Tumor Exosome Biomarker Co-recognitions Based Nanoliquid Biopsy for the Accurate Early Diagnosis of Pancreatic Cancer.

Pancreatic cancer, with extremely limited treatment options and poor prognosis, urgently needs a breakthrough in early diagnosis and monitoring. Tumor exosomes (T-Exos) detection is presently one of the most clinically significant liquid biopsy approaches for non-invasive pancreatic cancer early diagnosis, which, unfortunately, cannot be applied as a routine diagnostic tool until a number of obstacles, such as unsatisfactory specificity and sensitivity, as well as labor-intensive purification and analysis procedures by ultracentrifugation and enzyme-linked immunosorbent assay, are overcome. Here, we report a facile nanoliquid biopsy assay for the especially specific, ultrasensitive yet economical T-Exos detection by a dual specific biomarker antigen co-recognition and capturing strategy, which is enabled by grafting two corresponding capture antibodies on magnetic nanoparticles and gold nanoparticles, for the accurate detection of target tumor exosomes. This approach exhibits excellent specificity and ultrahigh sensitivity of detecting as low as 78 pg/mL pancreatic cancer exosome specific protein GPC1. Successful screening of 21 pancreatic cancer samples from 22 normal control cases with the enhanced specificity and sensitivity ensures the promising non-invasive monitoring and diagnosis for early stage pancreatic cancer.

Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

One-step multiplex analysis of breast cancer exosomes using an electrochemical strategy assisted by gold nanoparticles.

Exosomes, as a non-invasive biomarker, perform an important role in breast cancer screening and prognosis monitoring. However, establishing a simple, sensitive, and reliable exosome analysis technique remains challenging. Herein, a one-step multiplex analysis electrochemical aptasensor based on a multi-probe recognition strategy was constructed to analyze breast cancer exosomes. HER2-positive breast cancer cell (SK-BR-3) exosomes were selected as the model targets and three aptamers including CD63, HER2 and EpCAM aptamers were used as the capture units. Methylene blue (MB) functionalized HER2 aptamer and ferrocene (Fc) functionalized EpCAM aptamer, which were modified on gold nanoparticles (Au NPs), i.e. MB-HER2-Au NPs and Fc-EpCAM-Au NPs, were used as signal units. When the mixture of target exosomes, MB-HER2-Au NPs and Fc-EpCAM-Au NPs were added on the CD63 aptamer modified gold electrode, two Au NPs modified by MB and Fc could be specifically captured on the electrode by the recognition of three aptamers with target exosomes. Then one-step multiplex analysis of exosomes was achieved by detecting two independent electrochemical signals. This strategy can not only distinguish breast cancer exosomes from other exosomes (including normal exosomes and other tumor exosomes) but also HER2-positive breast cancer exosomes and HER2-negative breast cancer exosomes. Besides, it had high sensitivity and can detect SK-BR-3 exosomes with a concentration as low as 3.4×103 particles mL-1. Crucially, this method can be applicable to the examination of exosomes in complicated samples, which is anticipated to afford assistance for the screening and prognosis of breast cancer.

Synthetic miR-26a mimics delivered by tumor exosomes repress hepatocellular carcinoma through downregulating lymphoid enhancer factor 1.

The dysregulation of exosomal microRNAs plays an important role in the progression of hepatocarcinogenesis. In this study, we investigated the therapeutic potential of synthetic exosomal miR-26a against HCC cells and explored the feasibility of tumor-derived exosomes as drug delivery vehicles. Proliferation and migration assays were performed to examine the effects of miR-26a on HCC in vitro. The direct target gene of miR-26a was identified through miRecords analysis and target validation. The transferringefficiency and anti-HCC effect of exosomes with different origin were studied and the optimal miR-26a delivery method was established and verified in vitro and in vivo. In addition, the relationships between prognosis of HCC patients and miR-26a expression in HCC serum and exosomes were retrospectively analyzed. Here, we found that tumor cell-derived exosomes were taken in preferentially by HCC cells and promoted HCC progression through Wnt pathway by low-density lipoprotein receptor-related protein 6 (LRP6). HCC cells with vacuolar protein sorting-associated protein 35 knocked down were adopted to generate engineered LRP6-exosomes. The engineered HCC-derived exosomes loading miR-26a inhibited HCC progression in vitro and in vivo effectively. Overexpression of miR-26a impaired the growth and migration of HCC by targeting lymphoid enhancer factor 1 (LEF1). Moreover, low expression of exosomal miR-26a was an independent prognostic factor for recurrence and survival in HCC patients. Our findings suggested the exosomal miR-26a could serve as a non-invasive prognostic marker for HCC patients. Genetically modified tumor-derived exosomes showed preferable transfection efficiency but reduced Wnt activity, which provides a novel therapeutic strategy for HCC.

Accurate Capture and Identification of Exosomes: Nanoarchitecture of the MXene Heterostructure/Engineered Lipid Layer.

Recently, exosome detection has become an important breakthrough in clinical diagnosis. However, the effective capture and accurate identification of cancer exosomes in a complex biomatrix are still a tough task. Especially, the large size and non-conductivity of exosomes are not conducive to highly sensitive electrochemical or electrochemiluminescence (ECL) detection. Therefore, we have developed a Ti3C2Tx-Bi2S3-x heterostructure/engineered lipid layer-based nanoarchitecture to overcome the limitations. The engineered lipid layer not only specifically captured and efficiently fused CD63 positive exosomes but also showed excellent antifouling property in the biological matrix. Moreover, the MUC1 aptamer-modified Ti3C2Tx-Bi2S3-x heterostructure further identified and covered the gastric cancer exosomes that have been trapped in the engineered lipid layer. In the self-luminous Faraday cage-type sensing system, the Ti3C2Tx-Bi2S3-x heterostructure with sulfur vacancies extended the outer Helmholtz plane and amplified the ECL signal. Therefore, this sensor can be used to detect tumor exosomes in ascites of cancer patients without additional purification. It provides a new pathway to detect exosomes and other large-sized vesicles with high sensitivity.